2.4.14.1 Alginate
The naturally occurring alginate polymers have great potential in drug formulation because of their extensive application as food additives and their recognized lack of toxicity. Alginate is a historic term used in many applications such as the cosmetic and pharmaceutical industries. As this group of polymers possess numerous characteristics that makes it useful as a formulation aid, both as a conventional excipient and more specifically as a tool in polymeric-controlled drug delivery. The alginates were discovered by a British Pharmacist, E.C.C. Stanford; commercial production started in 1929. The annual production of alginates in the world is about 30 000 tonnes. Alginic acid and it’s salts (Ca, Mg, Na and K) are abundantly present in brown algae (pheophyta) of the genera macrocystis, laminaria, ascophyllum, alario, ecklonia, eisenia, nercocystis, sargassum, cystoseira, and fucus. Acetylated alginates are also isolated from some bacteria genera pseudomonas and acetobacter. Red algae belonging to the family coralenacease also contain these substances. Alginate are used in nanoparticles, grafted donor sites in burns, wound dressing and in recycling of textile dye [212].
2.4.14.2 Carrageenans and Red Seaweed
Carrageenans are marine hydrocolloids obtained by extraction from some members of the class rhodophyceae. The carrageenans are a group of related linear and sulfated polymers. The most important members of this class are Chondrus crispus and Gigartina stellata. Carrageenans were mainly used as gelling and thickening agents. Only a few studies have dealt with carrageenans for controlled release tablets. These studies dealt only with drug delivery from tablets on a hydraulic press or from tablets that contain the carrageenans in a mixture with other excipients. A polysaccharide obtained from edible red seaweeds (Chondrus crispus). It is used in pharmaceutical formulations and cosmetics. As an anticoagulant, antithrombotic, antiviral, antitumor, immunomodulatory, immobiliser, and cleaning of industrial effluents. Unlike alginate, carrageenan use is dominated by food applications, particularly in concentration with milk like products. Carrageenans are used in gelling and thickening toothpaste, microencapsulation and immobilization. Carrageenan is used as a grafted copolymer in food packaging and coating applications [213].
2.4.14.3 Agar and Agarose
A polysaccharide produced commercially from red algae blonging to the family Rhodophyceae particullay from Gelidium and Gracilaria. Agar polysaccharide is composed of neutral polysaccharide (agarose), charged polysaccharide (agaropectin), and highly sulfated galactans. It is used as a food additive in icings, glazes, processed cheese, jelly, sweets and marshmallows. Agar is used for growing microorganisms while most species are unable to degrade it. Agar is resistant to high temperature, can form brittle gels and can hold a large number of soluble solids. It used as gelling, thickening, stabilizing and viscosity controlling agent for jellies, candies and jams.
It shows also many medical, pharmaceutical and industrial applications such as a laxative, an anti-rheumatic agent and for making dental impressions. Agarose is a neutral polysaccharide in agar and is used mainly in the separation of biological macromolecules. Also, it has antioxidative, antibacterial, antimutagenic and immune modulating activities.
2.5 Biopolymer Type Number 4: Organic Polyoxoesters
Poly(3-hydroxyalkanoates) (PHAs) are structurally simple macromolecules. PHAs accumulate as discrete granules to levels as high as 90% of the cell dry weight and are generally believed to play a role as a sink for carbon and reducing equivalents [35, 37]. Most of the well identified PHAs are linear, head-to-tail polyesters composed of 3-hydroxy fatty acid monomers (Figure 2.3). In these polymers, the carboxyl group of one monomer forms an ester bond with the hydroxyl group of another monomer. In 1976, Imperial Chemical Industries (ICI) in England started to produce P(3HB) by fermentation. In 1993, Zeneca Bioproducts started their production business, later in 1996 Monsanto bought the production business from Zeneca. Using R. eutropha about 800 tons per year of P(3HB-co-3HV) produced under the trademark BiopolTM. Monsanto terminated its activities in this area by the end of 1998. Today many other companies remain still active in research and development of PHAs like Procter and Gamble as well as Metabolix (USA) and others all over the world. Biodegradable materials are often used within the biomedical field as implants or as drug carrier systems. Early inteest in environmentally friendly bioplastics was by the European environmental legislation in 2005
Figure 2.3 Chemical structures of PHAs. (1) General structural of PHAs. (2) The copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) P(3HB-co-3HV) as example of short chain length polymer (SCL). (3) P(HHX-co-HO-co-HD-co-HDD-co-….) as an example for PHAMCL.
[37, 214]. PHA was proved to be biocompatible and can be used in tissue engineering, implantations, and so on. Retinal pigment epithelium cells grow well on P(3HB-co-3HV) as a monolayer for their subretinal transplantation. PHA can be melted or solution processed into a variety of forms. Salt leaching, dip coating and thermally induced phase separation were used to produce scaffolds for cardiovascular tissue engineering. When seeded with cells and cultured in vitro, these scaffolds were used to create living tissue implants [215].
The hydroxyl-substituted carbon atom has R configuration in all characterized PHAs. At the C-3 atom (β position), an alkyl group length can vary from methyl (C1) to tridecyl (C13) [216]. This alkyl side chain is not necessarily saturated. Unsaturated, aromatic, epoxidized, halogenated, and branched monomers were reported as well [217]. Cross-linking of unsaturated bond substations in the side chains of PHAs can be added chemically [218]. Lütke-Eversloh et al. was the first to report on producing biopolymers with thioester linkages in the polymer backbone using C. necator in media containing 3-mercaptopropionate (3MP) or 3-mercaptobutyrate (3MB) in addition to 3-hydroxybutyrate as constituents [219–221]. Many factors affect the PHA’s chemical composition like the microbial strain, the substrate, the cultivation condition, the extraction method, the number of phaC, phaB genes, the regulator phaP (phasin) and the presence of inhibitors. They inhibit different pathways, especially those which supply the synthases with different kinds of monomer or inhibit other pathways, which consume these monomers for their own or degrade it to shorter units like β oxidation pathway. In general, the PHA composition depends on the PHA synthases, the carbon source and the metabolic routes involved. The molecular weights of PHAs were established by light scattering, gel permeation chromatograph and sedimentation analysis. Their monomer composition was determined by gas chromatography (GC), mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analysis [222]. PHAs show material properties that are similar to some common plastics such as polypropylene [223]. The bacterial origins of the PHAs make these polyesters a natural material, and many microorganisms have the ability to degrade these macromolecules [224]. The molecular mass of PHAs varies per PHA producer but is generally in the order of 50 × 103 to 1 × 106 Da. Inside the cell, P(3HB) exists in a fluid, amorphous state. However, after extraction from the cell with organic solvents, P(3HB) becomes highly crystalline [225] and in this state it is stiff but brittle material. Because of its brittleness, P(3HB) is not very stress resistant. The high melting temperature of P(3HB) (around 170 oC) is close to the temperature in which this polymer decomposes thermally and thus limits the ability to process the homopolymer. The incorporation of 3-hydroxyvalerate (3HV) into the P(3HB) resulted in P(3HB-co-3HV) copolymer that is less stiff and brittle than P(3HB), that can be used to prepare films that exert excellent water and gas barrier properties like polypropylene, and that can be processed at lower temperature while retaining most of the other excellent mechanical properties of P(3HB) [226]. (P(3HB-co-3HV)) has also low crystallinity and is more elastic than P(3HB) [227, 228]. The latex-like PHAs (PHAMCL) display
